Characterization and manipulation of feeding-related neural circuits

Abstract

This thesis contributed to building bridges between different levels of understanding in current neuroscience research on regulation of feeding related behavior: we aimed to show the translational value of rodents studies for human studies, thereby building a bridge between preclinical and clinical neuroscience research, as well as to build a bridge between microscopic and macroscopic approaches and results, by applying and, if possible, combining both. By doing so, we integrated knowledge about underlying molecular and cellular working mechanisms with knowledge about organisation and functioning of neural networks. This expanded and deepened our understanding of how the brain regulates feeding related behavior. We found for example that activity in a brain region important for satiation, the insula, gradually increases upon repeated exposure to sugar, indicating that satiation is slowly built up upon repeated tasting. Besides, we developed a novel technique with which we can activate specific neural projections and measure the effect of this activation on the entire brain. This technique revealed the cellular base of the indirect measure of brain activity as measured with functional MRI. This knowledge can also be applied to human functional MRI data. By applying and combining other, microscopic and macroscopic, techniques, we substantiated current knowledge and gained new insights into the regulation of feeding behaviour, for example the nucleus accumbens, part of the reward system, mediates the motivational, but not the hedonic, aspects of salt appetite.